Aim The aim of this study was to identify potential safety concerns associated with Sacituzumab Govitecan (SG), an antibody-drug conjugate targeting trophoblastic cell-surface antigen-2, by analyzing real-world safety data from the largest publicly available worldwide pharmacovigilance database. Methods All data obtained from the FDA Adverse Event Reporting System (FAERS) database from the second quarter of 2020 to the fourth quarter of 2022 underwent disproportionality analysis and Bayesian analysis to detect and assess the adverse event signals of SG, considering statistical significance when the lower limit of the 95% CI >1, based on at least 3 reports. Results Total of 1072 cases were included. The main safety signals were blood and lymphatic system disorders ROR(95CI)=7.23 (6.43-8.14), gastrointestinal disorders ROR(95CI)=2.01 (1.81-2.22), and relative infection adverse events, such as neutropenic sepsis ROR(95CI)=46.02 (27.15-77.99) and neutropenic colitis ROR(95CI)=188.02 (120.09-294.37). We also noted unexpected serious safety signals, including large intestine perforation ROR(95CI)=10.77 (3.47-33.45) and hepatic failure ROR(95CI)=3.87 (1.45-10.31), as well as a high signal for pneumonitis ROR(95CI)=9.93 (5.75-17.12). Additionally, age sub-group analysis revealed that geriatric patients (>65 years old) were at an increased risk of neutropenic colitis ROR(95CI)=282.05 (116.36-683.66), neutropenic sepsis ROR(95CI)=101.11 (41.83-244.43), acute kidney injury ROR(95CI)=3.29 (1.36-7.94), and atrial fibrillation ROR(95CI)=6.91 (2.86-16.69). Conclusion This study provides crucial real-world safety data on SG, complementing existing clinical trial information. Practitioners should identify contributing factors, employ monitoring and intervention strategies, and focus on adverse events like neutropenic sepsis, large intestine perforation, and hepatic failure. Further prospective studies are needed to address these safety concerns for a comprehensive understanding and effective management of associated risks.